Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Lung Neoplasms

Carcinoma

Prostatic Neoplasms

Adenocarcinoma

Stomach Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Cholangiocarcinoma

Urinary Bladder Neoplasms

Uterine Cervical Neoplasms

Carcinoma, Renal Cell

Liver Neoplasms

Head and Neck Neoplasms

Skin Neoplasms

Mouth Neoplasms

Salivary Gland Neoplasms

Laryngeal Diseases

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Carcinoma, Mucoepidermoid

Mucoepidermoid Tumor

Rectal Neoplasms

Bile Duct Neoplasms

Tongue Neoplasms

Laryngeal Neoplasms

Urologic Neoplasms

Lip Neoplasms

Tonsillar Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Breast Diseases

Skin Diseases

Disease Attributes

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Stomach Diseases

Colorectal Neoplasms

Intestinal Neoplasms

Intestinal Diseases

Rectal Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Kidney Neoplasms

Kidney Diseases

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

Biliary Tract Neoplasms

Bile Duct Diseases

Biliary Tract Diseases

Neoplasms, Cystic, Mucinous, and Serous

Tongue Diseases

Otorhinolaryngologic Neoplasms

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Otorhinolaryngologic Diseases

Oropharyngeal Neoplasms

Pharyngeal Neoplasms

Pharyngeal Diseases

Stomach Cancer

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Bile Duct Cancer

Renal Cell Carcinoma

Oral Cancer

Adenocarcinoma of the Appendix

Tongue Cancer

Mucoepidermoid Carcinoma

All Drugs and Chemicals

Antibodies

Immunoglobulins

Mitogens

Six dose levels have been selected for evaluation in the Phase I part of the study: 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg of A166

HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) breast cancer. Treatment with A166 at recommended Phase II dose.

HER2 positive (Immunohistochemistry (IHC) 2+ with fluorescence in situ hybridization (FISH) confirmation and Immunohistochemistry (IHC) 3+) gastric cancer. Treatment with A166 at recommended Phase II dose.

HER2 low expressing (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) breast cancer. Treatment with A166 at recommended Phase II dose.

All cancers other than breast cancer with low HER2 expression (Immunohistochemistry (IHC) 1+ and IHC 2+ without fluorescence in situ hybridization (FISH) confirmation) and HER2 positive (IHC2+ with FISH confirmation and Immunohistochemistry (IHC) 3+) cancers other than breast and gastric cancer. Treatment with A166 at recommended Phase II dose.

A166 is an Antibody Drug Conjugate (ADC) targeting HER2 expressing cancer cells.

A166

Jordi Rodon Ahnert, MD, PhD

Open-label, Phase I-II, first-in-human (FIH) study for A166 monotherapy in HER2-expressing or amplified patients who progressed on or did not respond to available standard therapies. Patients must have documented HER2 expression or amplification. The patient must have exhausted available standard therapies. Patients will receive study drug as a single IV infusion. Cycles will continue until disease progression or unacceptable toxicity.

This is an open-label, Phase I-II, first-in-human (FIH) study for A166 as monotherapy in HER2-expressing patients who progressed on or did not respond to available standard therapies. Patients enrolled in this Phase III study must have documented HER2 positivity defined as positive on in situ hybridization (ISH) or next-generation sequencing (NGS) or HER2 expression, defined as at least 1+ by validated immunohistochemistry (IHC) test. The patient must be, in the judgment of the investigator, an appropriate candidate for experimental therapy after available standard therapies have ceased to provide clinical benefit for their disease. Patients will receive study drug as a single IV infusion at the prescribed dose level in each treatment cycle. Cycles will continue until disease progression or unacceptable toxicity. The study is divided into 2 parts (Phase I and Phase II).

Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene

A Phase I-II, FIH Study of A166 in Locally Advanced/Metastatic Solid Tumors Expressing Human Epidermal Growth Factor Receptor 2 (HER2) or Are HER2 Amplified That Did Not Respond or Stopped Responding to Approved Therapies

Number of patients with dose limiting toxicities

Klus Pharma Inc.

Melanoma

Carcinoma, Non-Small-Cell Lung

Carcinoma, Squamous Cell

Carcinoma, Hepatocellular

Squamous Cell Carcinoma of Head and Neck

Thoracic Neoplasms

Lung Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Colonic Diseases

Neoplasms, Squamous Cell

Clear Cell Renal Cell Carcinoma

Antineoplastic Agents

Trastuzumab

Antibodies, Monoclonal

Cetuximab

Immunomodulating Agents

Antineoplastic Agents, Immunological

FATE-NK100 as a monotherapy in subjects with advanced solid tumor malignancies.

FATE-NK100 in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, HER2+ advanced gastric cancer or other advanced HER2+ solid tumors.

Regimen C: FATE-NK100 in combination with cetuximab in subjects with advanced colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC), or other epidermal growth factor receptor 1 positive (EGFR1+) advanced solid tumors.

FATE-NK100 is a donor-derived NK cell product comprised of ex vivo activated effector cells with enhanced anti-tumor activity

FATE-NK100

Epidermal growth factor receptor inhibitor antineoplastic agent

Jeff Chou, MD

This is a Phase 1, single-dose, open-label, dose-escalation study. The study will be conducted in three parts (i.e. regimens) in an outpatient setting as follows:

* Regimen A: FATE-NK100 as a monotherapy in subjects with advanced solid tumor malignancies.
* Regimen B: FATE-NK100 in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 positive (HER2+) advanced breast cancer, HER2+ advanced gastric cancer or other advanced HER2+ solid tumors.
* Regimen C: FATE-NK100 in combination with cetuximab in subjects with advanced colorectal cancer (CRC) or head and neck squamous cell cancer (HNSCC), or other epidermal growth factor receptor 1 positive (EGFR1+) advanced solid tumors.

FATE-NK100 as Monotherapy and in Combination With Monoclonal Antibody in Subjects With Advanced Solid Tumors

The incidence of dose-limiting toxicity (DLT) within each dose cohort within the first 28 days after FATE-NK100 administration (ie, Day 1 through Day 29).

Objective-response rate (ORR): defined as the proportion of patients who achieve partial response (PR) or complete response (CR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at any time on study.

The PK of FATE-NK100, as assessed by the proportion of lymphocytes in peripheral blood that are of donor/product origin at the specified time points.

Fate Therapeutics

Antirheumatic Agents

Anti-Inflammatory Agents

Pembrolizumab

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Triamcinolone

Triamcinolone Acetonide

Triamcinolone hexacetonide

Triamcinolone diacetate

Bendamustine Hydrochloride

Clofarabine

Immune Checkpoint Inhibitors

Lymphodepletion followed by TAC01-HER2 as a single IV infusion, with a potential for a second dose administration.

Lymphodepletion followed by TAC01-HER2 as a single IV infusion, followed by pembrolizumab administration.

TAC01-HER2 and:

* fludarabine and cyclophosphamide, or
* clofarabine and cyclophosphamide, or
* bendamustine, or
* cyclophosphamide

TAC01-HER2

TAC01-HER2 plus pembrolizumab and:

* fludarabine and cyclophosphamide, or
* clofarabine and cyclophosphamide, or
* bendamustine, or
* cyclophosphamide

TAC01-HER2 plus pembrolizumab

TAC01-HER2 is a novel cell therapy that consists of genetically engineered autologous T cells expressing T-cell Antigen Coupler (TAC) that recognizes human epidermal growth factor receptor 2 (HER2). TAC directs T-cells to the targeted antigen (HER2), and once engaged with the target, activates them via the endogenous T cell receptor.

This is an open-label, multicenter Phase 1/2 study that aims to establish safety, maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), pharmacokinetic profile and efficacy of TAC01-HER2 as a monotherapy, and in combination with pembrolizumab, in subjects with HER2 positive gastric and gastroesophageal adenocarcinoma.

The TAC technology is a novel approach to modifying T cells, herein referred to as TAC T cells, and using them in the treatment of solid tumors. TAC T cells are produced through genetic engineering, incorporating TAC receptors into a patient's own T cells. This redirects these enhanced T cells to specific cancer antigens, and upon recognition, activates them through the natural signaling pathways of the endogenous TCR. In the TAC01-HER2 engineered T cell product; TAC T cells recognize the HER2 protein present on the surface of tumor cells, and eradicate them. Consequently, it is hypothesized TAC01-HER2 will be potentially safe and effective in treating patients with HER2+ solid tumors and provide a clinically meaningful therapeutic benefit in patient populations with high unmet medical need.

This is a first-in-human study investigating TAC01-HER2 to evaluate the safety, MTD or RP2D, PK, and efficacy in subjects with HER2+ solid tumors who have been treated after at least 2 lines of prior therapy in Phase 1 and after at least 2 lines and no more than 4 lines of prior therapy in Phase 2.

In Phase 1, escalating doses of TAC01-HER2 will be evaluated to identify the RP2D using the classic keyboard design method. The monotherapy arm will treat all subjects with HER2-positive solid tumors that meet the eligibility criteria (completed). The combination arm will treat all 2+ or 3+ HER2-positive subjects with gastric or gastroesophageal AC who meet the eligibility criteria.

In Phase 2, dose expansion groups will further evaluate the efficacy, safety, and PK of the MTD or RP2D for TAC01-CLDN18.2 in subjects with gastric and esophageal adenocarcinoma. In Phase 2, a Simon 3-stage design will be used to enroll up to 36 subjects in Group A (monotherapy arm) and 34 subjects in Group B (combination arm).

In summary:

* Phase I monotherapy arm: Dose escalation in any HER2-positive solid tumor (completed).
* Phase I combination therapy arm: Dose escalation in combination with pembrolizumab in 2+ or 3+ HER2-positive gastric and gastroesophageal adenocarcinoma
* Phase II: Dose expansion cohorts: 2+ or 3+ HER2-positive gastric or gastroesophageal adenocarcinoma treated with TAC01-HER2 as a monotherapy (Group A) or in combination with pembrolizumab (Group B).

In Phase 1, escalating doses of TAC01-HER2 will be evaluated to identify the RP2D of the monotherapy arm and the combination arm using the classic keyboard design. In Phase 2, dose expansion groups will further evaluate the safety, efficacy, and PK of the MTD or RP2D for TAC01-HER2 as a monotherapy and in combination with pembrolizumab in subjects with gastric and gastroesophageal adenocarcinoma.

TAC T-cells for the Treatment of HER2-positive Solid Tumors

A Phase 1/2 Trial Investigating the Safety and Efficacy of Autologous TAC T Cell Monotherapy, and TAC T Cells in Combination With Pembrolizumab, in Relapsed HER2-Positive Solid Tumors

Document incidence of DLTs; Type, frequency, and severity of AEs (including clinically significant laboratory abnormalities).

Defined as the percentage of treated subjects with a complete or partial response (CR or PR) as assessed by imaging using Response Evaluation Criteria in Solid Tumors (RECIST)Version 1.1.

Defined as time from first response to disease progression, end of study, start of another anticancer therapy, or death

Defined as time from infusion to death from any cause

Defined as the percentage of treated subjects with stable disease (SD), PR, and CR as assessed by imaging using Response Evaluation Criteria in Solid Tumors (RECIST)Version 1.1.

Defined as time from infusion to disease progression or death from any cause

Document incidence of Dose-Limiting Toxicities.

Document type, frequency, and severity of AEs (including clinically significant laboratory abnormalities).

Defined as the maximum concentration of TAC T cells after infusion; assessed by vector copy number

Defined as the the first study day the Cmax is reached; assessed by vector copy number

Calculated using the trapezoid rule; assessed by vector copy number

Defined as the time between the first measurement of transgene above the limit of detection until the last observed quantifiable level of transgene; assessed by vector copy number

Correlation of HAMA detection with TAC PK and subject response

Correlation with adverse events and subject response

Merck Sharp & Dohme LLC

Triumvira Immunologics, Inc.

Esophageal Neoplasms

Esophageal Cancer

Fluorouracil

Nivolumab

Oxaliplatin

Ipilimumab

Week 1-12 Trastuzumab 6mg/kg d1 every 3 weeks (loading dose 8mg/kg) Nivolumab 1mg/kg i.v. d1 every 3 weeks Ipilimumab 3mg/kg i.v. d1 every 3 weeks Week 13 till EOT (max treatment period 12 months) Trastuzumab 4mg/kg d1 every 2 weeks Nivolumab 240mg i.v. d1 every 2 weeks

Trastuzumab 4mg/kg d1 every 2 weeks (loading dose 6mg/kg) Nivolumab 240mg i.v. d1 every 2 weeks mFOLFOX6 every 2 weeks Oxaliplatin at a dose of 85 mg/m2 IV over two hours (day 1) 5-FU 400 mg/m2 IV bolus (day 1) LV at a dose of 400 mg/m2 iv over two hours (day 1) 5-FU at a dose of 2400 mg/m2 IV over 46 hours (day 1-3)

Max Treatment period 12 months

Addition of Nivolumab to Standard therapy (chemotherapy and Trastuzumab)

Chemo-free immunotherapy with Nivolumab, Ipilimumab, Trastuzumab

Alexander Stein, Dr.

The INTEGA study assesses therapy Options for advanced or metastatic esophagogastric Adenocarcinoma in patients overexpressing human epidermal receptor type 2 (HER2 positive patients). Current treatment options in this situation include chemotherapy based palliative treatment in combination withTrastuzumab.

Recent studies have shown that immunotherapy with Nivolumab or Ipilimumab after previous chemotherapy can also improve survival in esophagogastric cancer.

This study assesses the efficacy of two experimental first line treatment strategies: A) Chemo-free immunotherapy with Trastuzumab, Nivolumab and Ipilimumab and B) addition of Nivolumab to the standard regimen (FOLFOX chemotherapy and Trastuzumab).

Gastric cancer is the fifth most common cancer in the world, and the third leading cause of cancer death in both sexes worldwide.

Surgical resection is currently the only curative treatment option for gastric cancer; however, \~50% of patients have metastatic disease at the time of diagnosis and chemotherapy is the mainstay of palliation in this setting.

Trastuzumab, in combination with chemotherapy, significantly improved survival in patients with overexpression of HER2.

In regard of the very limited therapeutic landscape of HER2 positive EGA, compared to breast cancer, further treatment options to relevantly improve the outcome is warranted. The integration of check-point inhibitors (e.g. Nivolumab, Ipilimumab) into the first line setting either within a chemotherapy-free combination arm or within an intensified standard arm of FOLFOX and trastuzumab with nivolumab may be able to improve the current limited survival of median 14 months.

Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in HER2 Positive EsophagoGastric Adenocarcinoma

Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in Previously Untreated HER2 Positive Locally Advanced or Metastatic EsophagoGastric Adenocarcinoma

Overall survival including milestone rate at 12 months

according to Common Terminology Criteria for Adverse Events and to the obtained data on vital signs, clinical parameters and feasibility of the regimen

Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

Response Rate (RR) according to RECIST v1.1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of A166 in Patients With Relapsed/Refractory Cancers Expressing HER2 Antigen or Having Amplified HER2 Gene	NCT03602079	HER2-positive B... HER2 Gene Mutat... HER-2 Gene Ampl... HER2 Positive G... Salivary Gland ... Salivary Gland ... Salivary Gland ... Salivary Gland ... Lung Cancer Colo-rectal Can... Rare Diseases Solid Tumor Recurrent Gastr... Recurrent Colon... Recurrent Breas... Head and Neck C... Head and Neck C... Bladder Cancer Cervical Cancer Liver Cancer Bile Duct Cance... Urologic Cancer Pancreatic Canc... Prostate Cancer Recurrent Prost... Rectal Cancer Recurrent Ovari... Recurrent Renal... Rectal Cancer S... Rectal Cancer S... Rectal Cancer S... Skin Cancer Mouth Cancer Lip Cancer Stag... Tongue Cancer Breast Neoplasm... Larynx Cancer Tonsil Cancer Palate Cancer Mucoepidermoid ... Primary Periton... Mucinous Adenoc... Mucinous Breast... Cholangiocarcin...	A166	18 Years -	Klus Pharma Inc.
FATE-NK100 as Monotherapy and in Combination With Monoclonal Antibody in Subjects With Advanced Solid Tumors	NCT03319459	HER2 Positive G... Colorectal Canc... Head and Neck S... EGFR Positive S... Advanced Solid ... HER2-positive B... Hepatocellular ... Non Small Cell ... Renal Cell Carc... Pancreatic Canc... Melanoma	FATE-NK100 Cetuximab Trastuzumab	18 Years -	Fate Therapeutics
TAC T-cells for the Treatment of HER2-positive Solid Tumors	NCT04727151	HER2 Positive G... Metastatic HER2...	TAC01-HER2 TAC01-HER2 plus...	18 Years -	Triumvira Immunologics, Inc.
Ipilimumab or FOLFOX in Combination With Nivolumab and Trastuzumab in HER2 Positive EsophagoGastric Adenocarcinoma	NCT03409848	Gastric Cancer Esophageal Canc... Adenocarcinoma ... HER2 Positive G... Metastatic Gast... GastroEsophagea...	Nivolumab Nivolumab Ipilimumab	18 Years -	AIO-Studien-gGmbH

Spots Global Cancer Trial Database for her2 positive gastric cancer